PROJECT SUMMARY Conventional treatment for conductive hearing loss normally includes hearing aids or middle ear surgery, which restores movement or continuity of the ossicular chain. However, in cases where conventional surgery is unsuitable or unsuccessful, instead of relying on sound transduction via the normal path involving the ossicular chain and the oval window, round window (RW) stimulation has been attempted with some success. A current issue with RW stimulation is the large variability in efficacy of the device between patients. The effective coupling of the device to the RW membrane has a big influence on the transmission of motion from the device to the inner ear, and may therefore affect the success of an implant. Secondly, difference in the anatomy of inner ear structures may also affect the efficacy of a device by providing paths for acoustic leak along the cochlea. Therefore, understanding the variability and significance of middle ear anatomy (for device-RW coupling interface) and inner ear structures (to further fundamental scientific knowledge on RW stimulation) is essential in the effort to improve current devices. To achieve these goals, we have three main aims. We will comprehensively study the anatomy with cadaveric whole specimens as well as histological temporal bone slide sections in Aim 1. In Aim 2, we will develop and test an effective RW stimulation device that will safely and efficiently couple the device vibration to the inner-ear. This will be tested on cadaveric human temporal bones by measuring the stapes velocity and changes in inner ear pressures in response to the stimulation at the RW. Finally, in Aim 3, we will develop a computational model utilizing the calculated impedance obtained by our experiment measurements, to aid in understanding the mechanism of RW stimulation. This model will account for the impedances both in air conduction stimulation and RW stimulation. Overall, the proposed middle and inner ear research in fresh human cadaveric specimens will provide new and thorough understanding of the RW and develop a detailed impedance model of the human cochlea. The proposed research can lead to a safe and effective RW stimulation device that will improve hearing and quality of life for patients with conductive and mixed hearing loss.